Intramolecular cycloadditions produce bicyclic ring systems, with four or more new chiral centers, in a single step from acyclic precursors. This spectacular increase in complexity often occurs with high selectivity. Intramolecular cyclo-additions are potent techniques for the synthesis of natural products. Prior to our preliminary studies, known examples of intramolecular cycloadditions generally involved six Pi electrons. We have now discovered examples of intramolecular cycloadditions involving 10 Pi electrons, and propose to develop these intramolecular [6+4] and [8+2] cycloadditions into practical and efficient methods for the construction of natural products and analogs containing fused odd-membered rings, with control over stereoselectivity. Our goals are to determine how substituents, and the chains which connect the reactive units, influence reactivity and stereoselectivity in the reactions of fulvenyl-dienes, heptafulvenyl-alkenes, and activated fulvenyl-dienes. Fulvenyl-dienes undergo [6+4] cycloadditions to produce hydroazulens fused to a third ring at the 4 and 5 carbons, heptafulvenyl-alkenes undergo [8+2] cycloadditions to give hydroazulenes fused to a third ring at the 1 and 2 positions, and the planned [6+2] cycloaddition of activated fulvenyl-alkenes should provide either the linear or nonlinear tricyclopentanoid skeletons. All of these reactions may provide methods to produce cyclopentanes differentially and stereospecifically substituted at each of the five carbon atoms. A computational technique to predict the stereoselectivies of these and other intramolecular cycloadditions has been devised and will be perfected in this project. The utility of these novel intramolecular cycloadditions will be demonstrated by the synthesis of representative natural products chosen from hydroazulene (artabsin), tricyclic cyclopentanoid (hirsutene, isocomene) and various anticancer or tumor-promoting tetracyclic terpenes (kempane, phorbol).